Mercury (Hg)-induced sensory dysfunction is a worldwide problem, especially in cultures that rely on food from aquatic environments or are exposed to industrial sources of organomercurials, e.g., methylmercury (MeHg) or phenylmercury (PhHg). The primary route of fetal Hg exposure is maternal transfer; neurological damage is significant in the fetus due to greater sensitivity of developing neurons. The zebrafish is an excellent biomedical model because embryonic development stages occur external to the adult allowing even embryonic behavioral patterns to be evaluated as a function of toxicity. Thus, the effect of toxic agents on neural connections necessary for proper behavioral expression can be observed and lifelong effects after early embryonic Hg exposure can be monitored. This proposal is guided by the hypothesis that pre-hatch/prenatal Hg exposure during deemed periods of development will affect the function of sensory and/or neuromuscular junction neurons resulting in short- and long-term changes in reflex responses to specific environmental stimuli. Aims and Methods: 1) identify specific stages sensitive to both inorganic and organic Hg exposure (Hg concentration determined by ICP-MS on brain, muscle and gonad) on embryonic and larval reflex arc neuron development through optical sectioning techniques using confocal microscopy, 2) differentiate between effects on individual sensory afferent neurons to reflex control centers in the CNS, descending axons, and neuromuscular junction connections by examining specific reflex responses to sensory stimuli, e.g., vibrational and visual, and 3) identify long-term effects (adult stage) of early embryonic Hg exposure. Reflex reactions will be recorded using high-speed digital videography with images computer-analyzed for latency to respond, velocity of reflex, and velocity of escape swim. Each variable corresponds to a specific part of the reflex arc neural pathway, i.e., sensory afferents, neural input processing, signals to neural efferents, and motoneuron activation. Alterations will be correlated to changes in neural development as observed by comparisons to images generated by confocal microscopy. Studies will be conducted using Hg2+, MeHg, and PhHg to identify the relationship of chemical structure (inorganic vs. alkyl vs. aryl) to toxic outcome. Adult dietary exposure to Hg will determine rote of transgenerational effects, on embryonic development of neuronal systems critical to startle reflex response. Waterborne exposure to eggs will identify the effects of Hg by direct exposure at specific stages of development vs. exposure through continual yolk absorption of maternally-derived Hg. This study will mirror prospective studies on human populations over much shorter time periods.